Epidemiological studies on diverticular disease of the colon

Objective: The aims of this thesis were to evaluate if there is an association between diverticular disease and colorectal cancer (Paper I), to assess any genetic contribution to the occurrence of diverticular disease (Paper II), determine how common hospitalization and surgery for diverticular disease are in measures of admission rates, incidence rates and lifetime risk (Paper II), and to estimate mortality in diverticulitis patients, needing hospital care (Paper IV).

Methods: Swedish national registries were cross-linked through individual personal identification numbers. Data on admissions for diverticular disease and diverticulitis were retrieved from the National Patient Register. In Paper I, 41,037 colon cancer cases, registered in the Swedish Cancer Registry, were compared to matched colon cancer-free controls in concern of preceding admission for diverticular disease. In Paper II, including 104,452 twins in the Swedish Twin Registry, diverticular disease admissions were compared between monozygotic and dizygotic twins. Admission rates, incidence rates and lifetime risk for hospital admission for diverticular disease and diverticular disease surgery were analyzed in 95,049 individuals with diverticular disease admissions in Paper III, by using data from the Total Population Register in estimating risk sets. Survival analyses were used when comparing mortality in 83,461 patients with a first admission for diverticulitis with matched disease-free individuals, in Paper IV.

Results: Within the first 6 months after admission due to diverticular disease, odds ratios of having a colon cancer were up to 31.49 (95% CI 19.00-52.21). After the first year, there was no association between diverticular disease and colon cancer (Paper I). Odds ratio for diverticular disease admission given that the co-twin was affected/not affected, was higher in monozygotic twins compared to same-sex dizygotic twins (7.15 [95% CI 4.82-10.61] vs. 3.20 [95% CI 2.21-4.63]). Heritability was estimated to 40% (Paper II). Incidence rates for diverticular disease admission were 47.4 (95% CI 47.1-47.4) and for diverticular disease surgery 8.4 (95% CI 8.2-8.5) per 100,000 person-years. Corresponding admission rates were 70.8 (95% CI 70.4-71.2) and 8.7 (95% CI 8.6-9.9). Following an increase 1990-1994, rates remained rather constant thereafter. The estimated remaining lifetime risk for diverticular disease admission at the age of 30 was 3.1% in men and 5.0% in women (Paper III). Diverticulitis patients had a four times higher mortality compared to disease-free individuals in short term; the first 100 days after initial admission, Hazard Ratio (HR) 4.44 (95% CI 4.26-4.63). Within this time, 11.4% of patients receiving surgical treatment died. Among all diverticulitis patients, long term mortality, from day 101 to five years, was increased 11% (HR 1.11, 95% CI 1.09-1.13).

Conclusions: Hospitalization for diverticular disease is not associated with colon cancer after one year. The first 12 months after initial hospitalization is however highly associated with colon cancer. Therefore, colon cancer should be excluded after a first episode of suspected diverticulitis, due to the risk of misdiagnosing colon cancer as diverticulitis. Genetic influence is of importance in diverticular disease occurrence. The continuous increase of diverticular disease hospitalizations found in other studies are not present in Sweden. Diverticulitis patients have a significantly reduced survival compared to disease-free individuals, both in short- and long term.

List of scientific papers

I. Granlund J, Svensson T, Granath F, Hjern F, Ekbom A, Blomqvist P, et al. Diverticular disease and the risk of colon cancer - a population-based case-control study. Alimentary pharmacology & therapeutics. 2011;34(6):675-81.
https://doi.org/10.1111/j.1365-2036.2011.04782.x

II. Granlund J, Svensson T, Olen O, Hjern F, Pedersen NL, Magnusson PK, et al. The genetic influence on diverticular disease--a twin study. Alimentary pharmacology & therapeutics. 2012;35(9):1103-7.
https://doi.org/10.1111/j.1365-2036.2012.05069.x

III. Sköldberg F, Granlund J, Discacciati A, Hjern F, Schmidt PT, Olén O. Incidence and lifetime risk of hospitalization and surgery for diverticular disease – a nation-wide cohort study. [Submitted]

IV. Granlund J, Sköldberg F, Olén O, Hjern F, Svensson T, Søfteland Sandvei M, Discacciati A, Schmidt PT. Mortality in patients hospitalized for diverticulitis in Sweden – a national population-based cohort study. [Manuscript]